Summary
Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common subtypes of cutaneous T cell lymphomas (CTCL). Advanced-stage MF/SS have poor prognoses and may be refractory to multiple systemic treatments. These cases can be difficult to achieve and maintain complete response and there is a need for novel therapeutics. Inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway by Tenalisib presents one such emerging drug. We report a relapsed/refractory SS patient achieving complete remission using the combination of Tenalisib and Romidepsin and subsequently maintaining long-duration CR with Tenalisib monotherapy.


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References
Hristov AC, Tejasvi T, A Wilcox R (2021) Cutaneous T-cell lymphomas: 2021 update on diagnosis, risk-stratification, and management. Am J Hematol 96(10):1313–1328. https://doi.org/10.1002/ajh.26299
Alpdogan O, Kartan S, Johnson W, Sokol K, Porcu P (2019) Systemic therapy of cutaneous T-cell lymphoma (CTCL). Chin Clin Oncol 8(1):10. https://doi.org/10.21037/cco.2019.01.02
Lampson BL, Brown JR (2017) PI3Kδ-selective and PI3Kα/δ-combinatorial inhibitors in clinical development for B-cell non-Hodgkin lymphoma. Expert Opin Investig Drugs 26(11):1267–1279. https://doi.org/10.1080/13543784.2017.1384815
Huen A, Haverkos BM, Zain J et al (2020) Phase I/Ib Study of Tenalisib (RP6530), a Dual PI3K δ/γ Inhibitor in Patients with Relapsed/Refractory T-Cell Lymphoma. Cancers (Basel) 12(8):2293. Published 2020 Aug 15. https://doi.org/10.3390/cancers12082293
Horwitz SM, Koch R, Porcu P et al (2018) Activity of the PI3K-δ, γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma. Blood 131(8):888–898. https://doi.org/10.1182/blood-2017-08-802470
Safety and Efficacy of Tenalisib (RP6530) in Combination with Romidepsin in Patients with Relapsed/Refractory T-cell Lymphoma. Available online: https://clinicaltrials.gov/ct2/show/NCT03770000. Accessed 30 Apr 2022
Compassionate Use Study of Tenalisib (RP6530). Available online: https://clinicaltrials.gov/ct2/show/NCT03711604. Accessed 30 Apr 2022
Polansky M, Talpur R, Daulat S, Hosing C, Dabaja B, Duvic M (2015) Long-Term Complete Responses to Combination Therapies and Allogeneic Stem Cell Transplants in Patients With Sézary Syndrome. Clin Lymphoma Myeloma Leuk 15(5):e83–e93. https://doi.org/10.1016/j.clml.2014.09.013
Kim YH, Bagot M, Pinter-Brown L et al (2018) Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial [published correction appears in Lancet Oncol. 2018 Nov;19(11):e581]. Lancet Oncol 19(9):1192–1204. https://doi.org/10.1016/S1470-2045(18)30379-6
Beygi S, Duran GE, Fernandez-Pol S, Rook AH, Kim YH, Khodadoust MS (2022) Resistance to mogamulizumab is associated with loss of CCR4 in Cutaneous T-cell Lymphoma [published online ahead of print, 2022 Apr 18]. Blood blood.2021014468. https://doi.org/10.1182/blood.2021014468
Hughes CF, Khot A, McCormack C et al (2015) Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood 125(1):71–81. https://doi.org/10.1182/blood-2014-07-588236
Talpur R, Thompson A, Gangar P, Duvic M (2014) Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk 14(4):297–304. https://doi.org/10.1016/j.clml.2014.01.010
Carlo-Stella C, Delarue R, Scarfo L et al (2020) A First-in-human Study of Tenalisib (RP6530), a Dual PI3K δ/γ Inhibitor, in Patients With Relapsed/Refractory Hematologic Malignancies: Results From the European Study. Clin Lymphoma Myeloma Leuk 20(2):78–86. https://doi.org/10.1016/j.clml.2019.10.013
Iyer SP, Huen A, Ferreri AJM et al (2018) Pooled safety analysis and efficacy of Tenalisib (RP6530), a PI3K δ/γ inhibitor in patients with relapsed/refractory lymphoid malignancies. Blood 132:2925. https://doi.org/10.1182/blood-2018-99-112757
Iyer S, Huen A, Ai W et al (2021) Safety and efficacy of tenalisib given in combination with Romidepsin in patients with relapsed/refractory T-Cell Lymphoma: Final results from a phase I/II open label multi-center study. Blood (ASH Annual Meeting Abstracts)
Kaneda MM, Messer KS, Ralainirina N et al (2016) PI3Kγ is a molecular switch that controls immune suppression. Nature 539(7629):437–442. https://doi.org/10.1038/nature19834
Lewis J, Girardi M, Vakkalanka S, Viswanadha S, Bertoni F (2013) RP6530, a dual PI3Kδ/γ inhibitor, attenutates AKT phosphorylation and induces apoptosis in primary cutaneous T cell lymphoma (CTCL) cells. Blood 22:4418. https://doi.org/10.1182/blood.V122.21.4418.4418
Acknowledgements
AOH conceptualized the paper. SPI, MD, and AOH participated in patient care. CNN wrote the original manuscript draft. CNN, SPI, MD, PJB, AN, KVR, and AOH reviewed and edited the manuscript.
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This work was supported by Rhizen Pharmaceuticals AG, Basel, Switzerland.
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Nguyen, C.N., Iyer, S.P., Duvic, M. et al. Complete Response to tenalisib and romidepsin with long-term maintenance using tenalisib monotherapy in a patient with relapsed and refractory sézary syndrome. Invest New Drugs 41, 350–355 (2023). https://doi.org/10.1007/s10637-022-01315-6
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DOI: https://doi.org/10.1007/s10637-022-01315-6